Despite the advent of sophisticated imaging techniques over the last three decades, none of the available imaging techniques is entirely satisfactory for detection and monitoring progression of focal vascular disease. Most importantly, over the past twenty years, changes in the vessel wall elasticity as a result of disease have been proven to be a critical parameter in determining the progression of disease and the wall's propensity for rupture. However, imaging of such regional changes of vascular elasticity has been proven extremely challenging. The primary objective of the proposed study is thus to demonstrate that our ultrasound-based, ultra-high frame rate, elasticity imaging technique, i.e., Pulse Wave Imaging (PWI), is capable of accurate quantification of the vessel wall stiffness based on the mapping of pulse wave propagation along the vessel wall. The pulse wave velocity is directly related to stiffness and mapping it regionally at high temporal resolution allows for localized mechanical property estimation. Regional estimation of the stiffness allows thus detection, localization and diagnosis of the disease. In order to demonstrate the potential of the proposed technique in detection and early diagnosis of focal vascular disease and given the expertise of the team of investigators, the disease of abdominal aortic aneurysm, the most common aneurysm type and an often silent and deadly disease, will first be considered followed by atherosclerosis in mice. Secondary objectives will thus entail the establishment of the link between the changes in mechanical properties and aneurysm rupture in simulation, mice and human studies, and preliminary application of the technique in additional vascular disease cases. To address this urgent clinical need, the specific aims of the proposed study are to: 1) determine the PWI potential in detecting vascular wall stiffness in simulations and phantom experiments; 2) assess role and quality of PWI in qualitatively and quantitatively measuring vascular stiffness as a result of focal vascular disease presence and progression in vivo; 3) design and implement a real-time, customized PWI system, and perform preliminary clinical feasibility study. PWI can be easily integrated into the current clinical ultrasound protocol; thus, with no or minimal additional cost to healthcare. PUBLIC HEALTH RELEVANCE: Vascular stiffening happens naturally with aging. One of the results of vascular aging is also a higher probability of developing vascular diseases such as aneurysms and atherosclerosis. We propose a novel technique Pulse Wave Imaging (PWI) for direct estimation of vascular stiffness to follow disease progression and predict propensity for rupture.